Associations of Water Quality with Cholera in Case-Control Studies: A Systematic Review and Meta-Analysis

Cholera is a significant health risk for low- and middle-income countries (LMIC), and the threat of outbreaks is likely to increase due to climate change. To keep up to date with the link between water quality and cholera, we conducted a systematic review and meta-analysis to update a previous review. We searched Embase, Web of Science and PubMed for literature published between 2016 and 2022. Search terms were consistent with the previous review. Study quality was assessed using Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Exposures of water were categorized according to the WHO/UNICEF Joint Monitoring Program for Water Supply, Sanitation and Hygiene (JMP) and further divided by the service ladder. Odds ratios were extracted and pooled by performing random-effects meta-analysis. We identified 22 new eligible studies and analysed them together with the 45 studies included in the previous review. Analyses revealed higher odds of cholera when consuming sachet water (OR=1.69, 95% CI: 1.13 to 2.52), unimproved water (OR=2.91, 95% CI: 1.21 to 7.02), surface water (OR=3.40, 95% CI: 2.52 to 4.58), and untreated water (OR=2.51, 95% CI: 2.03 to 3.10). Meanwhile, treating water (OR=0.42, 95% CI: 0.27 to 0.65), by boiling (OR=0.38, 95% CI: 0.17 to 0.84) or chlorination (OR=0.37, 95% CI: 0.17 to 0.83), and drinking basic water (OR=0.44, 95% CI: 0.27 to 0.69) showed protection. Pooled estimates changed with updated evidence while qualitative insights on the protective or risk factors remain valid. Relatively low-cost methods like boiling or chlorinating water provide good protection comparable to providing basic water to the public. Systematic review registration: PROSPERO 2021 CRD42021271881 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported, in whole or in part, by Gavi, the Vaccine Alliance, Bowdoin College, and the Bill & Melinda Gates Foundation, via the Vaccine Impact Modelling Consortium (Grant Number OPP1157270 / INV-009125). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The dataset and R codes for generating figures and tables are available at the GitHub repository of the corresponding author: [https://github.com/kimfinale/Cholera\_WASH\_meta][1] [1]: https://github.com/kimfinale/Cholera_WASH_meta